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1.  Decreased Functional Brain Connectivity in Adolescents with Internet Addiction 
PLoS ONE  2013;8(2):e57831.
Background
Internet addiction has become increasingly recognized as a mental disorder, though its neurobiological basis is unknown. This study used functional neuroimaging to investigate whole-brain functional connectivity in adolescents diagnosed with internet addiction. Based on neurobiological changes seen in other addiction related disorders, it was predicted that connectivity disruptions in adolescents with internet addiction would be most prominent in cortico-striatal circuitry.
Methods
Participants were 12 adolescents diagnosed with internet addiction and 11 healthy comparison subjects. Resting-state functional magnetic resonance images were acquired, and group differences in brain functional connectivity were analyzed using the network-based statistic. We also analyzed network topology, testing for between-group differences in key graph-based network measures.
Results
Adolescents with internet addiction showed reduced functional connectivity spanning a distributed network. The majority of impaired connections involved cortico-subcortical circuits (∼24% with prefrontal and ∼27% with parietal cortex). Bilateral putamen was the most extensively involved subcortical brain region. No between-group difference was observed in network topological measures, including the clustering coefficient, characteristic path length, or the small-worldness ratio.
Conclusions
Internet addiction is associated with a widespread and significant decrease of functional connectivity in cortico-striatal circuits, in the absence of global changes in brain functional network topology.
doi:10.1371/journal.pone.0057831
PMCID: PMC3581468  PMID: 23451272
2.  Periarticular Osteoporosis Is a Prominent Feature in Early Rheumatoid Arthritis: Estimation Using Shaft to Periarticular Bone Mineral Density Ratio 
Journal of Korean Medical Science  2013;28(2):287-294.
We aimed to quantify periarticular osteoporosis and investigate its significance in 45 patients with rheumatoid arthritis (RA) and 106 controls. Dual-energy X-ray absorptiometry (DXA) was used to determine the ratio of shaft to periarticular bone mineral density (BMD) as an index of periarticular demineralization. Periarticular osteoporosis was measured by conventional radiography. The BMDs of shaft and periarticular regions in eight designated areas on proximal phalanges were quantified. Clinical variables were examined to identify risk factors for periarticular osteoporosis. The assessment of periarticular osteoporosis on X-ray images reached a moderate degree of interobserver agreement among four physicians (ĸ = 0.47). For BMD quantification, we designed three types of mathematical formulae: the ratio of shaft to periarticular BMD, the mean of the ratios, and the ratio of the sums. These ratios were significantly higher in the patients with early RA (disease duration ≤ 3 yr) than in controls (P < 0.01). The findings were not as distinctive in patients with established RA. Body mass index, cumulative dose of corticosteroid, and C-terminal telopeptide were correlated with BMD ratios. Conclusively, DXA-assisted localized quantification and BMD ratio calculations are feasible for assessing periarticular demineralization. Periarticular osteoporosis is a relatively distinctive feature of early RA.
doi:10.3346/jkms.2013.28.2.287
PMCID: PMC3565142  PMID: 23399828
Bone Density; Arthrits; Rheumatoid; Periarticular Osteopenia
3.  The Antiobesity Effect of Polygonum aviculare L. Ethanol Extract in High-Fat Diet-Induced Obese Mice 
The antiobesity effects of a P. aviculare ethanol extract (PAE) in high-fat diet- (HFD-) induced obese mice were investigated. The mice were fed an HFD or an HFD supplemented with PAE (400 mg/kg/day) for 6.5 weeks. The increased body weights, adipose tissue weight, and adipocyte area as well as serum total triglyceride, leptin, and malondialdehyde concentrations were decreased in PAE-treated HFD-induced obese mice relative to the same measurements in untreated obese mice. Furthermore, PAE significantly suppressed the elevated mRNA expression levels of sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor γ, fatty acid synthase, and adipocyte protein 2 in the white adipose tissue of obese mice. In addition, PAE treatment of 3T3-L1 cells inhibited adipocyte differentiation and fat accumulation in a dose-dependent manner. These results suggest that PAE exerts antiobesity effects in HFD-induced obese mice through the suppression of lipogenesis in adipose tissue and increased antioxidant activity.
doi:10.1155/2013/626397
PMCID: PMC3570948  PMID: 23431342
4.  IGFBP-3 Inhibits Cytokine-Induced Insulin Resistance and Early Manifestations of Atherosclerosis 
PLoS ONE  2013;8(1):e55084.
Metabolic syndrome is associated with visceral obesity, insulin resistance and an increased risk of cardiovascular diseases. Visceral fat tissue primarily consists of adipocytes that secrete cytokines leading to a state of systemic inflammation in obese conditions. One of the IGF-independent functions of IGFBP-3 is its role as an anti-inflammatory molecule. Our study in obese adolescents show a decrease in total IGFBP-3 levels and increase in proteolyzed IGFBP-3 in circulation when compared to their normal counterparts and establishes a positive correlation between IGFBP-3 proteolysis and adiposity parameters as well as insulin resistance. In human adipocytes, we show that IGFBP-3 inhibits TNF-α-induced NF-κB activity in an IGF-independent manner, thereby restoring the deregulated insulin signaling and negating TNF-α-induced inhibition of glucose uptake. IGFBP-3 further inhibits TNF-α, CRP and high glucose-induced NF-κB activity in human aortic endothelial cells (HAECs) and subsequently suppresses monocyte adhesion to HAEC through the IGFBP-3 receptor. In conclusion, these findings suggest that reduced levels of IGFBP-3 in circulation and reduced expression of IGFBP-3 in macrophages in obesity may result in suppression of its anti-inflammatory functions and therefore IGFBP-3 may present itself as a therapeutic for obesity-induced insulin resistance and for events occurring in the early stages of atherosclerosis.
doi:10.1371/journal.pone.0055084
PMCID: PMC3557269  PMID: 23383064
5.  Early Referral to a Nephrologist Improved Patient Survival: Prospective Cohort Study for End-Stage Renal Disease in Korea 
PLoS ONE  2013;8(1):e55323.
The timing of referral to a nephrologist may influence the outcome of chronic kidney disease patients, but its impact has not been evaluated thoroughly. The results of a recent study showing an association between early referral and patient survival are still being debated. A total of 1028 patients newly diagnosed as end-stage renal disease (ESRD) from July 2008 to October 2011 were enrolled. Early referral (ER) was defined as patients meeting with a nephrologist more than a year before dialysis and dialysis education were provided, and all others were considered late referral (LR). The relationship of referral pattern with mortality in ESRD patients was explored using a Cox proportional hazards regression models. Time from referral to dialysis was significantly longer in 599 ER patients than in 429 LR patients (62.3±58.9 versus 2.9±3.4 months, P<0.001). Emergency HD using a temporary vascular catheter was required in 485 (47.2%) out of all patients and in 262 (43.7%) of ER compared with 223 (52.0%) of LR (P = 0.009). After 2 years of follow-up, the survival rate in ER was better than that in LR (hazard ratio [HR] 2.38, 95% confidence interval [CI] 1.27–4.45, P = 0.007). In patients with diabetes nephropathy, patient survival was also significantly higher in ER than in LR (HR 4.74, 95% CI 1.73–13.00, P = 0.002). With increasing age, HR also increased. Timely referral to a nephrologist in the predialytic stage is associated with reduced mortality.
doi:10.1371/journal.pone.0055323
PMCID: PMC3555934  PMID: 23372849
6.  Susceptibility to air pollution effects on mortality in Seoul, Korea: A case-crossover analysis of individual-level effect modifiers 
Air pollution’s mortality effects may differ by subpopulation; however, few studies have investigated this issue in Asia. We investigated susceptibility to air pollutants on total, cardiovascular, and respiratory mortality in Seoul, Korea for the period 2000 – 2007. We applied time-stratified case-crossover analysis, which allows direct modeling of interaction terms, to estimate susceptibility based on sex, age, education, marital status, and occupation. An interquartile range increase in pollution was associated with odds ratios of 0.94 (95% confidence interval, 0.25 – 1.62), 2.27 (1.03–3.53), 1.94 (0.80 – 3.09), and 2.21 (1.00 – 3.43) for total mortality and 1.95 (0.64 – 3.27), 4.82 (2.18 – 7.54), 3.64 (1.46 – 5.87), and 4.32 (1.77 – 6.92) for cardiovascular mortality for PM10, nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO), respectively. Ozone effect estimates were positive, but not statistically significant. Results indicate that some populations are more susceptible than others. For total or cardiovascular mortality, associations were higher for males, those 65 – 74 years, and those with no education or manual occupation for some pollutants. For example, the odds ratio for SO2 and cardiovascular mortality was 1.19 (1.03 – 1.37) times higher for those with manual occupations than professional occupations. Our findings provide evidence that some populations are more susceptible to the effects of air pollution than others, which has implications for public policy and risk assessment for susceptible subpopulations.
doi:10.1038/jes.2012.6
PMCID: PMC3543153  PMID: 22395258
air pollution; effect modifiers; mortality; time-stratified case–crossover analysis; susceptible subpopulations
7.  Clinical Efficacy of Plasmapheresis in Patients with Neuromyelitis Optica Spectrum Disorder and Effects on Circulating Anti-Aquaporin-4 Antibody Levels 
Background and Purpose
Although plasmapheresis is becoming standard practice as a rescue therapy for neuromyelitis optica (NMO), evidence for the therapeutic efficacy of plasmapheresis is limited, and the effect of plasmapheresis on anti-aquaporin-4 (AQP4) levels in patients with NMO has not been reported. Here, our objective was to evaluate the clinical efficacy of therapeutic plasmapheresis and its effect on anti-AQP4 antibody levels in patients with NMO spectrum disorder (NMOSD).
Methods
We retrospectively reviewed the medical records of 15 patients with NMOSD who had 18 acute attacks and received plasmapheresis because they did not respond to high-dose intravenous methylprednisolone (IVMP) therapy. Anti-AQP4 antibodies were measured before and after plasmapheresis. The primary outcomes were functional improvements immediately and 6 months after plasmapheresis, and the secondary outcome was the change in anti-AQP4 antibody serum levels following plasmapheresis.
Results
Plasmapheresis following IVMP therapy led to significant improvement in 50% of the 18 attacks in 15 patients immediately after the procedure was completed, and in 78% (14 attacks) after 6 months. Plasmapheresis was generally well tolerated in all patients. Anti-AQP4 antibody serum levels declined significantly following plasmapheresis, to a mean of 15% of the preplasmapheresis levels. Lower scores on the visual outcome scale recorded before an attack were associated with significant immediate improvement upon the completion of plasmapheresis (p=0.03).
Conclusions
Plasmapheresis following IVMP therapy effectively removed anti-AQP4 antibodies and was accompanied by a substantial improvement in the neurological disability of patients with NMOSD. Lower levels of pre-existing neurological damage may be associated with an improved acute response to plasmapheresis.
doi:10.3988/jcn.2013.9.1.36
PMCID: PMC3543908  PMID: 23346159
plasmapheresis; neuromyelitis optica; anti-aquaporin-4 antibody
8.  Detection of Helicobacter pylori in Gastric Aspirates Using a Monoclonal Antibody-Based Test 
Gut and Liver  2012;7(1):30-34.
Background/Aims
The objective of this study was to evaluate a monoclonal antibody-based test to detect Helicobacter pylori-specific antigen in gastric aspirates from humans.
Methods
Sixty-one volunteers were enrolled in the study. All of the subjects underwent a 13C-urea breath test (UBT) before esophagogastroduodenoscopy. Gastric aspirates were analyzed for pH and ammonia and used for polymerase chain reaction (PCR), culture, and monoclonal antibody-based detection of H. pylori. Multiple biopsies of the gastric antrum and body were obtained for a rapid urease test (RUT) and histological evaluation.
Results
Thirty-six subjects were H. pylori-positive and 25 were H. pylori-negative according to the UBT results. Compared with the H. pylori-negative subjects, H. pylori-positive subjects had a higher pH (4.77±1.77 vs 3.49±1.30, p<0.05) and ammonia level (1,130.9±767.4 vs 184.2±126.3, p<0.0001). The sensitivities and specificities of the PCR test, RUT, culture test, and monoclonal antibody-based test were 100% and 72%, 89% and 100%, 47% and 100%, and 78% and 100%, respectively.
Conclusions
The monoclonal antibody-based test for diagnosing H. pylori infection in gastric aspirates has increased sensitivity compared with the culture test and specificity as high as that of the RUT. The test may be useful as an additive test for examining gastric aspirates.
doi:10.5009/gnl.2013.7.1.30
PMCID: PMC3572317  PMID: 23423538
Helicobacter pylori; Gastric aspirate; Monoclonal antibody-based test
9.  Grape-Seed Proanthocyanidin Extract as Suppressors of Bone Destruction in Inflammatory Autoimmune Arthritis 
PLoS ONE  2012;7(12):e51377.
Chronic autoimmune inflammation, which is commonly observed in rheumatoid arthritis (RA), disrupts the delicate balance between bone resorption and formation causing thedestruction of the bone and joints. We undertook this study to verify the effects of natural grape-seed proanthocyanidin extract (GSPE), an antioxidant, on chronic inflammation and bone destruction. GSPE administration ameliorated the arthritic symptoms of collagen-induced arthritis (CIA), which are representative of cartilage and bone destruction. GSPE treatment reduced the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and osteoclast activity and increased differentiation of mature osteoblasts. Receptor activator of NFκB ligand expression in fibroblasts from RA patients was abrogated with GSPE treatment. GSPE blocked human peripheral blood mononuclear cell-derived osteoclastogenesis and acted as an antioxidant. GSPE improved the arthritic manifestations of CIA mice by simultaneously suppressing osteoclast differentiation and promoting osteoblast differentiation. Our results suggest that GSPE may be beneficial for the treatment of inflammation-associated bone destruction.
doi:10.1371/journal.pone.0051377
PMCID: PMC3519627  PMID: 23251512
10.  Role of IL-15 in Sepsis-Induced Skeletal Muscle Atrophy and Proteolysis 
Background
Muscle wasting in sepsis is associated with increased proteolysis. Interleukin-15 (IL-15) has been characterized as an anabolic factor for skeletal muscles. Our study aims to investigate the role of IL-15 in sepsis-induced muscle atrophy and proteolysis.
Methods
Mice were rendered septic either by cecal ligation and puncture or by intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg i.p.). Expression of IL-15 mRNA and protein was determined by reverse transcriptase polymerase chain reaction and Western blot analysis in the control and septic limb muscles. C2C12 skeletal muscle cells were stimulated in vitro with either LPS or dexamethasone in the presence and absence of IL-15 and sampled at different time intervals (24, 48, or 72 hours). IL-15 (10µg/kg) was intraperitoneally administered 6 hours before sepsis induction and limb muscles were sampled after 24 hours of sepsis. Cathepsin L activity was determined to measure muscle proteolysis. Atrogin-1 and muscle-specific ring finger protein 1 (MuRF1) expressions in limb muscle protein lysates was analyzed.
Results
IL-15 mRNA expression was significantly lower in the limb muscles of septic mice compared to that of controls. Cathepsin L activity in C2C12 cells was significantly lower in presence of IL-15, when compared to that observed with individual treatments of LPS or dexamethasone or tumor necrosis factor α. Further, the limb muscles of mice pre-treated with IL-15 prior to sepsis induction showed a lower expression of atrogin-1 and MuRF1 than those not pre-treated.
Conclusion
IL-15 may play a role in protection against sepsis-induced muscle wasting; thereby, serving as a potential therapeutic target for sepsis-induced skeletal muscle wasting and proteolysis.
doi:10.4046/trd.2012.73.6.312
PMCID: PMC3538184  PMID: 23319993
Interleukin-15; Muscular Atrophy; Proteolysis; Muscle Retardation; Sepsis
11.  IL-17-deficient allogeneic bone marrow transplantation prevents the induction of collagen-induced arthritis in DBA/1J mice 
Experimental & Molecular Medicine  2012;44(11):694-705.
IL-17-producing CD4+ T cells (Th17) play important functions in autoimmune diseases and allograft rejection of solid organs. We examined the effects of IL 17 and its mechanism of action on arthritis in a murine collagen-induced arthritis (CIA) model using bone marrow transplantation (BMT) system. DBA/1J mice were administered a lethal radiation dose and then rescued with bone marrow derived from either wild-type (WT) or IL-17-/- mice on C57BL/6 background mice. CIA was induced after the bone marrow transplant, and disease progression was characterized. DBA/1J mice with CIA that received IL-17-/- donor bone marrow showed potently inhibited development and severity of clinical arthritis as compared with CIA mice that received WT bone marrow. Reduced secretion of the pro-inflammatory cytokines tumor necrosis factor-α, IL-1β, and IL-6, and collagen-specific T cell responses were observed in mice that received IL-17-/- bone marrow. IL-17 blockade also inhibited effector T cell proliferation by reciprocally regulating the Treg/Th17 ratio. IL-17 blockade prevented joint destruction in mice with CIA. These findings suggest that CIA with BMT is a viable method of immunological manipulation and that IL-17 deficiency suppresses severe joint destruction and inflammation in CIA mice. There may be clinical benefits in blocking IL-17 and BMT in the treatment of rheumatoid arthritis.
doi:10.3858/emm.2012.44.11.078
PMCID: PMC3509186  PMID: 23114425
arthritis, experimental; bone marrow transplantation; interleukin-17; Th17 cells; T-lymphocytes, regulatory; transplantation, homologous
12.  Burden of Disease of Multiple Sclerosis in Korea 
Epidemiology and Health  2012;34:e2012008.
OBJECTIVES
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. There are few reports on the burden of disease of MS, worldwide. The authors aim to estimate burden of disease and estimate the epidemiologic indexes of MS in Korea using available epidemiologic data.
METHODS
Epidemiologic indexes were computed using DISMOD II software based on prevalence from nationwide survey, incidence estimated from extrapolation, mortality from National Statistics Office, and duration of disease from literature as input indexes. We calculated disability-adjusted life year (DALY) as a measure of premature mortality and disability, equivalent to years of healthy life lost due to a given condition.
RESULTS
The incidence of MS in Korea was 0.1 per 100,000, higher in female than in male. The highest incidence was estimated in the age group between 35 and 44 years in male and age group between 25 and 29 years in female. Total burden of disease of MS was 1,394 DALY, comprised of 292 (21%) years of life lost and 1,101 (79%) years lived with disability. The mean age at onset of MS was 33 years old in men and 32 years old in female. Estimated duration of disease was 35 years in men and 40 years in female. Most of the DALY of MS occurred in the adult population between 25 and 54 years of age.
CONCLUSION
Although MS is a rare disease in Korea, most of the DALY arises from young people, which results in a major financial burden on the patient, family, health system and society.
doi:10.4178/epih/e2012008
PMCID: PMC3521103  PMID: 23251838
Multiple sclerosis; Burden of disease; DISMOD II; Incidence; Prevalence; Quality of Life
13.  Epidemiological Characteristics of Novel Influenza A (H1N1) in Antiviral Drug Users in Korea 
PLoS ONE  2012;7(10):e47634.
Soon after the first novel influenza A (H1N1) death was documented in Korea on August 15, 2009, prompt treatment with antiviral drugs was recommended when an infection was suspected. Free antiviral drugs were distributed to patients who met the case definition in the treatment guidelines, and patients prescribed the antiviral drugs were included in the Antiviral Drug Surveillance System (ADSS). A total of 2,825,821 patients were reported to the ADSS from September 1 to December 31, 2009. Odds ratios were calculated to compare the risks of severe diseases, as indicated by general hospital admissions or intensive care unit (ICU) admissions according to demographic characteristics, underlying medical conditions, and behavioral factors. Approximately 6% of the total population received antiviral drugs during the study period. Of these, 2,709,611 (95.9%) were outpatients, 114,840 (4.06%) were hospitalized, and 1,370 (0.05%) were admitted to the ICU. Children aged 0–9 yr accounted for 33.94% of all reported cases, whereas only 3.89% of the patients were ≥ 60 yr. The estimated incidence of novel influenza A (H1N1) during the pandemic was 5.68/100 of all reported cases. Mortality due to influenza A (H1N1) during the pandemic was 0.33/100,000, with the highest mortality of 1.31/100,000 for patients aged ≥ 60 years. Severe pandemic H1N1 influenza was associated with the presence of one or more underlying medical conditions in elderly aged ≥ 60 years and with lower economic status. Moreover, influenza A (H1N1) appeared to be age-specific in terms of mortality. Although the incidence and admission rates of influenza A (H1N1) were higher in younger age groups, fatal cases were much more likely to occur in the elderly (≥60 years). In contrast to earlier influenza A (H1N1) reports, the risks of a severe outcome were elevated among those who were underweight (body mass index < 18.5 kg/m2).
doi:10.1371/journal.pone.0047634
PMCID: PMC3474727  PMID: 23082184
14.  Posterior Interspinous Fusion Device for One-Level Fusion in Degenerative Lumbar Spine Disease : Comparison with Pedicle Screw Fixation - Preliminary Report of at Least One Year Follow Up 
Objective
Transpedicular screw fixation has some disadvantages such as postoperative back pain through wide muscle dissection, long operative time, and cephalad adjacent segmental degeneration (ASD). The purposes of this study are investigation and comparison of radiological and clinical results between interspinous fusion device (IFD) and pedicle screw.
Methods
From Jan. 2008 to Aug. 2009, 40 patients underwent spinal fusion with IFD combined with posterior lumbar interbody fusion (PLIF). In same study period, 36 patients underwent spinal fusion with pedicle screw fixation as control group. Dynamic lateral radiographs, visual analogue scale (VAS), and Korean version of the Oswestry disability index (K-ODI) scores were evaluated in both groups.
Results
The lumbar spine diseases in the IFD group were as followings; spinal stenosis in 26, degenerative spondylolisthesis in 12, and intervertebral disc herniation in 2. The mean follow up period was 14.24 months (range; 12 to 22 months) in the IFD group and 18.3 months (range; 12 to 28 months) in pedicle screw group. The mean VAS scores was preoperatively 7.16±2.1 and 8.03±2.3 in the IFD and pedicle screw groups, respectively, and improved postoperatively to 1.3±2.9 and 1.2±3.2 in 1-year follow ups (p<0.05). The K-ODI was decreased significantly in an equal amount in both groups one year postoperatively (p<0.05). The statistics revealed a higher incidence of ASD in pedicle screw group than the IFD group (p=0.029).
Conclusion
Posterior IFD has several advantages over the pedicle screw fixation in terms of skin incision, muscle dissection and short operative time and less intraoperative estimated blood loss. The IFD with PLIF may be a favorable technique to replace the pedicle screw fixation in selective case.
doi:10.3340/jkns.2012.52.4.359
PMCID: PMC3488645  PMID: 23133725
Degenerative; Fusion device; Interspinous; Lumbar disease; Posterior; Adjacent segmental degeneration
15.  Extracorporeal Shock Wave Therapy in Myofascial Pain Syndrome of Upper Trapezius 
Annals of Rehabilitation Medicine  2012;36(5):675-680.
Objective
To evaluate the effect of extracorporeal shock wave therapy (ESWT) in myofascial pain syndrome of upper trapezius with visual analogue scale (VAS) and pressure threshold by digital algometer.
Method
Twenty-two patients diagnosed with myofascial pain syndrome in upper trapezius were selected. They were assigned to treatment and standard care (control) groups balanced by age and sex, with eleven subjects in each group. The treated group had done four sessions of ESWT (0.056 mJ/mm2, 1,000 impulses, semiweekly) while the control group was treated by the same protocol but with different energy levels applied, 0.001 mJ/mm2. The VAS and pressure threshold were measured twice: before and after last therapy. We evaluated VAS of patients and measured the pressure threshold by using algometer.
Results
There were two withdrawals and the remaining 20 patients were three men and 17 women. Age was distributed with 11 patients in their twenties and 9 over 30 years old. There was no significant difference of age, sex, pre-VAS and pre-pressure threshold between 2 groups (p>0.05) found. The VAS significantly decreased from 4.91±1.76 to 2.27±1.27 in the treated group (p<0.01). The control group did not show any significant changes of VAS score. The pressure threshold significantly increased from 40.4±9.94 N to 61.2±12.16 N in the treated group (p<0.05), but there was no significant change in the control group.
Conclusion
ESWT in myofascial pain syndrome of upper trapezius is effective to relieve pain after four times therapies in two weeks. But further study will be required with more patients, a broader age range and more males.
doi:10.5535/arm.2012.36.5.675
PMCID: PMC3503943  PMID: 23185732
Extracorporeal shock wave therapy; Myofascial pain syndrome; Upper trapezius; Visual analogue scale; Pressure threshold
16.  Regression of syndesmophyte after bone marrow transplantation for acute myeloid leukemia in a patient with ankylosing spondylitis: a case report 
Introduction
Disease progression of ankylosing spondylitis has been considered irreversible. However, we report a case of spontaneous regression of syndesmophyte development following allogeneic peripheral blood stem cell transplantation in a patient with acute myeloid leukemia, who was also diagnosed as having ankylosing spondylitis. To the best of our knowledge, this is the first case report presenting the partial radiologic regression of syndesmophytes.
Case presentation
A 39-year-old man with active ankylosing spondylitis achieved clinical remission and partial radiological regression of cervical spine syndesmophytes following a peripheral blood stem cell transplantation for acute myeloid leukemia. Our patient received an allogeneic peripheral blood stem cell transplantation following a pre-transplantation conditioning regimen of total body irradiation and cyclophosphamide. The donor was a human leukocyte antigen-matched 29-year-old man. Our patient has remained asymptomatic and has received no medication for ankylosing spondylitis for nearly three years.
Conclusions
Several explanations are proposed for the regression of syndesmophytes and clinical improvement in active ankylosing spondylitis observed in our patient, including changes in bone remodeling and immune reconstitution following stem cell transplantation, the effect of immunosuppressive agents, or fluctuation in the natural course of ankylosing spondylitis although further studies are required. The regression of syndesmophytes in ankylosing spondylitis in this case raises the possibility that stem cell transplantation might contribute to the development of a novel therapeutic strategy for treatment of the disease.
doi:10.1186/1752-1947-6-250
PMCID: PMC3459693  PMID: 22909092
17.  Preoperative predictors of malignant gastric submucosal tumor 
Purpose
The preoperative prediction of malignant potential in patients with gastric submucosal tumors (SMTs) plays an important role in decisions regarding their surgical management.
Methods
We evaluated the predictors of malignant gastric SMTs in 314 patients with gastric SMTs who underwent surgery in Chonnam National University Hospital.
Results
The malignant SMTs were significantly associated with age (odds ratio [OR], 1.067; 95% confidence interval [CI], 1.042 to 1.091; P < 0.0001), presence of central ulceration (OR, 2.690; 95% CI, 1.224 to 5.909; P = 0.014), and tumor size (OR, 1.791; 95% CI, 1.483 to 2.164; P < 0.0001). Receiver operating characteristic curve analysis showed that tumor size was a good predictor of malignant potential. The most relevant predictor of malignant gastric SMT was tumor size with cut-offs of 4.05 and 6.40 cm.
Conclusion
Our findings indicated that age, central ulceration, and tumor size were significant preoperative predictors of malignant SMTs. We suggest that 4 cm be selected as a threshold value for malignant gastric SMTs. In patients with a gastric SMT larger than 4 cm with ulceration, wide resection of the full thickness of the gastric wall or gastrectomy with adequate margins should be performed because of its malignant potential.
doi:10.4174/jkss.2012.83.2.83
PMCID: PMC3412188  PMID: 22880181
Stomach neoplasms; Submucosal tumor; Malignant factor; Preoperative predictor
18.  Clinicopathological Features of Female Gastric Carcinoma Patients with Curative Resection: Comparison with Male Patients 
Chonnam Medical Journal  2012;48(2):86-90.
Little is known about the clinicopathological features of female gastric carcinoma (FGC) patients. We compared the clinicopathologic features and outcomes of FGC patients with curative resection with those of male gastric carcinoma (MGC) patients. We reviewed the hospital records of 940 FGC patients between 1986 and 2005 at Chonnam National University Hospital. Multivariate analysis showed that presence of serosal invasion, lymph node metastasis, and operative type were significant prognostic factors for survival of FGC patients with curative resection. Furthermore, the overall 5-year survival rate of FGC patients with curative resection (53.4%) was higher than that of MGC patients (47.6%, p<0.05). In advanced cases, no significant difference was observed in the overall 5-year survival rate between the FGC and MGC patients (41.6% vs 37.4%, p>0.05). Therefore, serosal invasion, lymph node metastasis, and type of operation were statistically significant parameters associated with survival. Early detection is more important for improving the prognosis of female patients with gastric cancer than for male patients.
doi:10.4068/cmj.2012.48.2.86
PMCID: PMC3434796  PMID: 22977748
Female gastric carcinoma; Prognosis; Early detection of cancer
19.  Obesity aggravates the joint inflammation in a collagen-induced arthritis model through deviation to Th17 differentiation 
Experimental & Molecular Medicine  2012;44(7):424-431.
White fat cells secrete adipokines that induce inflammation and obesity has been reported to be characterized by high serum levels of inflammatory cytokines such as IL-6 and TNF-α. Rheumatoid arthritis (RA) is a prototype of inflammatory arthritis, but the relationship between RA and obesity is controversial. We made an obese inflammatory arthritis model: obese collagen-induced arthritis (CIA). C57BL/6 mice were fed a 60-kcal high fat diet (HFD) from the age of 4 weeks and they were immunized twice with type II collagen (CII). After immunization, the obese CIA mice showed higher arthritis index scores and histology scores and a more increased incidence of developing arthritis than did the lean CIA mice. After treatment with CII, mixed lymphocyte reaction also showed CII-specific response more intensely in the obese CIA mice than lean CIA. The anti-CII IgG and anti-CII IgG2a levels in the sera of the obese CIA mice were higher than those of the lean CIA mice. The number of Th17 cells was higher and the IL-17 mRNA expression of the splenocytes in the obese CIA mice was higher than that of the lean CIA mice. Obese CIA mice also showed high IL-17 expression on synovium in immunohistochemistry. Although obesity may not play a pathogenic role in initiating arthritis, it could play an important role in amplifying the inflammation of arthritis through the Th1/Th17 response. The obese CIA murine model will be an important tool when we investigate the effect of several therapeutic target molecules to treat RA.
doi:10.3858/emm.2012.44.7.047
PMCID: PMC3406287  PMID: 22513335
arthritis, experimental; inflammation; mice; obesity; Th17 cells
20.  A NAC transcription factor and SNI1 cooperatively suppress basal pathogen resistance in Arabidopsis thaliana 
Nucleic Acids Research  2012;40(18):9182-9192.
Transcriptional repression of pathogen defense-related genes is essential for plant growth and development. Several proteins are known to be involved in the transcriptional regulation of plant defense responses. However, mechanisms by which expression of defense-related genes are regulated by repressor proteins are poorly characterized. Here, we describe the in planta function of CBNAC, a calmodulin-regulated NAC transcriptional repressor in Arabidopsis. A T-DNA insertional mutant (cbnac1) displayed enhanced resistance to a virulent strain of the bacterial pathogen Pseudomonas syringae DC3000 (PstDC3000), whereas resistance was reduced in transgenic CBNAC overexpression lines. The observed changes in disease resistance were correlated with alterations in pathogenesis-related protein 1 (PR1) gene expression. CBNAC bound directly to the PR1 promoter. SNI1 (suppressor of nonexpressor of PR genes1, inducible 1) was identified as a CBNAC-binding protein. Basal resistance to PstDC3000 and derepression of PR1 expression was greater in the cbnac1 sni1 double mutant than in either cbnac1 or sni1 mutants. SNI1 enhanced binding of CBNAC to its cognate PR1 promoter element. CBNAC and SNI1 are hypothesized to work as repressor proteins in the cooperative suppression of plant basal defense.
doi:10.1093/nar/gks683
PMCID: PMC3467076  PMID: 22826500
21.  Spot Urine Albumin to Creatinine Ratio and Serum Cystatin C are Effective for Detection of Diabetic Nephropathy in Childhood Diabetic Patients 
Journal of Korean Medical Science  2012;27(7):784-787.
Spot urinary albumin to creatinine ratio (ACR) measurement has been suggested as a surrogate to 24-hr urine collection for the assessment of microalbuminuria, and cystatin C (cysC) is known as an advantageous marker for renal function. The aim of this study was to evaluate the clinical values of spot urinary ACR and serum cysC for the assessment of diabetic nephropathy instead of 24-hr urine microalbumin in children and adolescents with diabetes. A total of 113 children and adolescents (age 12-19 yr, M:F = 47:66) with type 1 or 2 diabetes were enrolled. We evaluated the validity of spot urine ACR and serum cysC, and then compared them to 24-hr urine microalbumin and creatinine clearance. Spot urine ACR was correlated with 24-hr urine albumin excretion (R2 = 0.828, P = 0.001) and creatinine clearance (R2 = 0.249, P = 0.017). The ROC curve analysis of serum cysC demonstrated higher diagnostic accuracy than that of serum creatinine (AUC 0.732 vs 0.615). Both the measurements of spot urine ACR and serum cysC might better predict the presence of diabetic nephropathy than 24-hr urine microalbumin in childhood diabetic patients.
doi:10.3346/jkms.2012.27.7.784
PMCID: PMC3390728  PMID: 22787375
Diabetic Nephropathies; Albumin to Creatinine Ratio; Cystatin C; Childhood Diabetes
22.  Air Pollution and Symptoms of Depression in Elderly Adults 
Environmental Health Perspectives  2012;120(7):1023-1028.
Background: Although the effect of air pollution on various diseases has been extensively investigated, few studies have examined its effect on depression.
Objectives: We investigated the effect of air pollution on symptoms of depression in an elderly population.
Methods: We enrolled 537 participants in the study who regularly visited a community center for the elderly located in Seoul, Korea. The Korean version of the Geriatric Depression Scale-Short Form (SGDS-K) was used to evaluate depressive symptomatology during a 3-year follow-up study. We associated ambient air pollutants with SGDS-K results using generalized estimating equations (GEE). We also conducted a factor analysis with items on the SGDS-K to determine which symptoms were associated with air pollution.
Results: SGDS-K scores were positively associated with interquartile range (IQR) increases in the 3-day moving average concentration of particulate matter with an aerodynamic diameter ≤ 10 μm (PM10) [17.0% increase in SGDS-K score, 95% confidence interval (CI): 4.9%, 30.5%], the 0–7 day moving average of nitrogen dioxide [NO2; 32.8% (95% CI: 12.6%, 56.6%)], and the 3-day moving average of ozone [O3; 43.7% (95% CI: 11.5%, 85.2%)]. For these three pollutants, factor analysis showed that air pollution was more strongly associated with emotional symptoms such as feeling happy and satisfied than with somatic or affective symptoms.
Conclusions: Our study suggests that increases in PM10, NO2, and O3 may increase depressive symptoms among the elderly. Of the symptoms evaluated, ambient air pollution was most strongly associated with emotional symptoms.
doi:10.1289/ehp.1104100
PMCID: PMC3404652  PMID: 22514209
air pollution; depressive symptoms; elderly; factor analysis; panel study
23.  The Influence of Nutritional Assessment on the Outcome of Ostomy Takedown 
Purpose
Ostomy takedown is often considered a simple procedure without intention; however, it is associated with significant morbidity. This study is designed to evaluate factors predicting postoperative complications in the ostomy takedown in view of metabolism and nutrition.
Methods
A retrospective, institutional review-board-approved study was performed to identify all patients undergoing takedown of an ostomy from 2004 to 2010.
Results
Of all patients (150), 48 patients (32%; male, 31; female, 17) had complications. Takedown of an end-type ostomy showed a high complication rate; complications occurred in 55.9% of end-type ostomies and 15.7% of loop ostomies (P < 0.001). Severe adhesion was also related to a high rate of overall complication (41.3%) (P = 0.024). In preoperative work-up, ostomy type was not significantly associated with malnutrition status. However, postoperatively severe malnutrition level (albumin <2.8 mg/dL) was statistically significant in increasing the risk of complications (72.7%, P = 0.015). In particular, a significant postoperative decrease in albumin (>1.3 mg/dL) was associated with postoperative complications, particularly surgical site infection (SSI). Marked weight loss such as body mass index downgrading may be associated with the development of complications.
Conclusion
A temporary ostomy may not essentially result in severe malnutrition. However, a postoperative significant decrease in the albumin concentration is an independent risk factor for the development of SSI and complications.
doi:10.3393/jksc.2012.28.3.145
PMCID: PMC3398110  PMID: 22816058
Ostomy takedown; Malnutrition; Albumins; Surgical site infection; Complication
24.  Ethanol Extract of Dianthus chinensis L. Induces Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells In Vitro 
Dianthus chinensis L. is used to treat various diseases including cancer; however, the molecular mechanism by which the ethanol extract of Dianthus chinensis L. (EDCL) induces apoptosis is unknown. In this study, the apoptotic effects of EDCL were investigated in human HepG2 hepatocellular carcinoma cells. Treatment with EDCL significantly inhibited cell growth in a concentration- and time-dependent manner by inducing apoptosis. This induction was associated with chromatin condensation, activation of caspases, and cleavage of poly (ADP-ribose) polymerase protein. However, apoptosis induced by EDCL was attenuated by caspase inhibitor, indicating an important role for caspases in EDCL responses. Furthermore, EDCL did not alter the expression of bax in HepG2 cells but did selectively downregulate the expression of bcl-2 and bcl-xl, resulting in an increase in the ratio of bax:bcl-2 and bax:bcl-xl. These results support a mechanism whereby EDCL induces apoptosis through the mitochondrial pathway and caspase activation in HepG2 cells.
doi:10.1155/2012/573527
PMCID: PMC3356935  PMID: 22645629
25.  Osteoporotic profiles in elderly patients with symptomatic lumbar spinal canal stenosis 
Indian Journal of Orthopaedics  2012;46(3):279-284.
Background:
The osteoporosis and lumbar canal stenosis, in elderly patients are under diagnosed and under reported. We report a cross sectional study to demonstrate the osteoporotic profile in patients with lumbar spinal stenosis (LSS) and to determine the proportion of patients with LSS who need to be treated for osteoporosis.
Materials and Methods:
One hundred and six postmenopausal patients with symptomatic LSS were evaluated for osteoporotic profile, which included lumbar and hip bone mineral density (BMD), serum vitamin D concentration, bone resorption and formation markers. Demographic and disease related variables were analyzed to identify the association with the risk of osteoporosis or osteopenia. Statistical analysis used were multivariate logistic regression with a forward stepwise procedure.
Results:
Twenty-four patients (22.6%) had osteoporosis and 60 (56.6%) had osteopenia. Overall, 84 patients (79.2%) with symptomatic LSS had osteoporosis or osteopenia. Fifty-nine patients (55.6%) had hypovitaminosis D. All bone turnover makers [alkaline phosphatase, osteocalcin, urinary-N-terminal telopeptide (u-NTx)] were demonstrated to be within normal range. Only age was associated with the risk of osteoporosis or osteopenia in the hip region. In the lumbar spine, all variables were not associated with osteoporosis or osteopenia. 44 patients (41.5%) required treatment for osteoporosis as per risk factors for osteoporosis. According to the guidelines from the Health Insurance Review Agency, however, only 20 patients (18.8% required) qualified for reimbursement for osteoporosis medications.
Conclusions:
LSS is associated with osteopenia, osteoporosis, and hypovitaminosis D, which should prompt careful screening and treatment in cases of osteoporosis and osteoarthritis.
doi:10.4103/0019-5413.96379
PMCID: PMC3377137  PMID: 22719113
Bone mineral density; bone turnover marker; hypovitaminosis D; lumbar spinal stenosis; osteoporosis

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